Methods and compositions for treating pancreatic cancer

Abstract

Methods and compositions related to treating pancreatic cancer are described.

1 . A method of treating pancreatic cancer in a subject in need thereof, comprising:
 inhibiting C/EBP homologous protein (CHOP) in pancreatic β cells by administering to the subject a composition comprising:   (a) a CHOP inhibiting moiety, and   (b) a pancreatic β cell targeting moiety.   
     
     
         2 . A method of treating pancreatic cancer by regulating C/EBP homologous protein (CHOP) in pancreatic β cells, the method comprising administering a nucleic acid composition comprising:
 (a) a CHOP inhibiting moiety, and 
 (b) a pancreatic β cell targeting moiety that directs the CHOP inhibiting moiety to its target in a pancreatic cell. 
 
     
     
         3 . The method of  claim 1 , wherein the CHOP inhibiting moiety is a nucleic acid. 
     
     
         4 . The method of  claim 1 , wherein the CHOP inhibiting moiety and the pancreatic β cell targeting moiety are operably linked. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the pancreatic β cell targeting moiety is a peptide. 
     
     
         10 . The method of  claim 9 , wherein the peptide is internalized by a pancreatic cell. 
     
     
         11 . The method of  claim 9 , wherein the peptide is glucagon-like peptide 1 (GLP-1), or a fragment thereof. 
     
     
         12 . The method of  claim 1 , wherein the CHOP inhibiting moiety is a nucleic acid editing moiety. 
     
     
         13 . The method of  claim 12 , wherein the nucleic acid editing moiety is a genomic DNA editing moiety. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the pancreatic β cell targeting moiety comprises a guiding nucleic acid sequence. 
     
     
         17 . The method of  claim 16 , wherein the CHOP inhibiting moiety and/or the pancreatic β cell targeting moiety is inducible by an inducer. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the administering comprises administering to a subject systemically. 
     
     
         24 . The method of  claim 1 , wherein the administering reduces or alleviates pancreatic β cell ER stress. 
     
     
         25 .- 60 . (canceled) 
     
     
         61 . A method of inhibiting pancreatic adenocarcinoma (PDAC) growth in a subject comprising, administering a treatment comprising a pharmaceutical composition wherein the pharmaceutical composition comprises:
 (a) a CHOP inhibiting moiety, and   (b) a pancreatic β cell targeting moiety, and wherein the administering of the treatment inhibits C/EBP homologous protein (CHOP) in pancreatic β cell and further, wherein the inhibition of CHOP alleviates effects of β cell dysfunction.   
     
     
         62 . (canceled) 
     
     
         63 . The method of  claim 61 , wherein the effects of β cell dysfunction comprise initiation and progression of PDAC. 
     
     
         64 . The method of  claim 2 , wherein the CHOP inhibiting moiety is a nucleic acid. 
     
     
         65 . The method of  claim 2 , wherein the CHOP inhibiting moiety and the pancreatic 3 cell targeting moiety are operably linked. 
     
     
         66 . The method of  claim 2 , wherein the pancreatic β cell targeting moiety is a peptide. 
     
     
         67 . The method of  claim 66 , wherein the peptide is internalized by a pancreatic cell.